Front Matter

(Rick Simeone) #1

106 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder


Oxytocin and Developmental Neurological Disorders


Many reviews have exhaustively described the involvement of oxytocin in
learning and memory, and in shaping and regulating the social brain. We
believe one of the best reviews is by Grinevich et al. [10]. The strongest line
of evidence supporting the oxytocin system in social behavior, feeding
behavior, and maternal care has been generated via the study of knockout
mice in which either the oxytocin or the oxytocin receptor genes are inacti-
vated (Table 4.1). Mice constitutively lacking oxytocin (Oxt−/−) are unable
to release milk and have impaired social memory [85]. Mice with constitu-
tive ablation of the oxytocin receptor gene (Oxtr−/−) display a behavior very
similar to that of a mouse where oxytocin producing neurons had been
depleted. These animals display social deficits. In addition, although learn-
ing is normal in mice where the oxytocin receptor gene has been deleted
(Oxtr−/− mice), reversal learning is strongly decreased, indicating impaired
cognitive flexibility suggestive of ASD [86]. Importantly, even a 50% loss of

Table 4.1 Abnormal compartments in ASD that share the loci of oxytocin receptors.

Brain region Autistic abnormalities

Amygdala 13–16% enlargement; functional magnetic resonance imaging study
showed that patients with autism did not activate the amygdala when
making mentalistic inferences from the eyes, whilst people without autism
did show amygdala activity
Olfactory Individuals with ASD exhibited impaired, intact, or increased odor
sensitivity. Abnormal responses to tastes, cold, heat, pain, tickle, and itch
were also observed
Nucleus
accumbens

This is involved in reward anticipation and appears to be defective in ASD

BNST BNST processes information and readiness for response to a threat by
maintaining information from a vast connectivity network. Anatomically,
the BNST is sexually dimorphic; it may explain the gender disparity in the
prevalence and treatment of stress‐related psychiatric diseases and as such
should be investigated as a possible target for treatments. Indeed, drug
targets already involve subpopulations of receptors abundant in the BNST
such as serotonin
Periform
cortex

Cytoarchitecture changes in olfactory cortex may underlie olfactory
differences and sensory deficits seen in autism; increased glial cells
Caudate
nucleus

Increased volume of caudate nucleus (enlargement) in medication naïve
individuals
BNST, bed nucleus of the stria terminalis.
Source: Adapted from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341354/table/T4/.
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